Yao Ting, Hu Weiwei, Chen Jinmei, Shen Leer, Yu Yongsheng, Tang Zhenghao, Zang Guoqing, Zhang Yi, Chen Xiaohua
Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
J Gastrointest Oncol. 2022 Oct;13(5):2472-2484. doi: 10.21037/jgo-22-299.
Hepatocellular carcinoma (HCC) is a malignant cancer with rapid progression, vascular invasion, a high recurrence rate and poor prognosis, so it is necessary to take early measures to halt this process. Accumulating evidence indicates that collagen XV (translated by Col15a1) is a basement membrane molecule related to tumour metastasis in several organs. However, the potential function of collagen XV in the liver associated with HCC remains to be further elucidated.
Col15a1 was overexpressed in HepG2 and HCCLM3 cells. CCK8 and colony formation assays were used to assess the capacity of cell proliferation, and Transwell and wound healing assays were utilized to measure cell migration. Western blotting and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) quantified the protein and mRNA expression levels of genes related to the epithelial-mesenchymal transition (EMT). Then, the effect of collagen XV on tumour metastasis was confirmed . Finally, we inhibited discoidin domain receptor 1 (DDR1) via DDR1-IN-1 to explore whether the collagen XV interacted with DDR1 to regulate EMT.
Patients of HCC with higher expression of Col15a1 showed better survival than patients with low expression. Overexpression of collagen XV in HepG2 and HCCLM3 cells suppressed cell proliferation and migration and inhibited pulmonary and liver metastasis . In addition, collagen XV downregulated the DDR1 and transcription factor (Snail, Slug), regulated the EMT markers (Vimentin, E-cadherin, N-cadherin, and MMP9). Furthermore, inhibition of the DDR1 receptor by DDR1-IN-1 suppressed the gene promoting the EMT.
Collagen XV functioned as a metastasis inhibitor in HCC by regulating the DDR1-Snail/Slug axis to regulate EMT.
肝细胞癌（HCC）是一种进展迅速、具有血管侵袭性、高复发率且预后较差的恶性肿瘤，因此有必要尽早采取措施来阻止这一进程。越来越多的证据表明，胶原蛋白XV（由Col15a1翻译）是一种与多个器官肿瘤转移相关的基底膜分子。然而，胶原蛋白XV在与HCC相关的肝脏中的潜在功能仍有待进一步阐明。
在HepG2和HCCLM3细胞中过表达Col15a1。采用CCK8和集落形成试验评估细胞增殖能力，利用Transwell和伤口愈合试验测量细胞迁移。蛋白质免疫印迹法和实时定量逆转录聚合酶链反应（qRT-PCR）对上皮-间质转化（EMT）相关基因的蛋白质和mRNA表达水平进行定量。然后，证实了胶原蛋白XV对肿瘤转移的影响。最后，我们通过DDR1-IN-1抑制盘状结构域受体1（DDR1），以探究胶原蛋白XV是否与DDR1相互作用来调节EMT。
Col15a1高表达的HCC患者比低表达患者的生存期更长。在HepG2和HCCLM3细胞中过表达胶原蛋白XV可抑制细胞增殖和迁移，并抑制肺和肝转移。此外，胶原蛋白XV下调DDR1和转录因子（Snail、Slug），调节EMT标志物（波形蛋白、E-钙黏蛋白、N-钙黏蛋白和基质金属蛋白酶9）。此外，DDR1-IN-1抑制DDR1受体会抑制促进EMT的基因。
胶原蛋白XV通过调节DDR1-Snail/Slug轴来调节EMT，从而在HCC中发挥转移抑制作用。
